The Experimental Studies of the Protection of α-lipoic Acid Against Lung Injury Induced by Acute Necrotic Pancreatitis in Rats
|Course||Department of Gastroenterology,|
|Keywords||acute necrotic pancreatitis acute lung injury NF-κB α-lipoic acid|
Objective: To investigate the protection and mechanism ofα-lipoic acid(ALA) on lung injury induced by acute necrotic pancreatitis(ANP) in rats and the mechanism.Methods: Fifty-four Sprague-Dawley rats were randomly allocated into three groups: the control group, acute necrotic pancreatitis group and ALA-pretreated group.The model of ANP was induced by the retrograde injection of 5% sodium taurocholate in the pancreatic duct.The control group animals were executed operation,but nothing was injected,pancreas was just flipped gently.ALA(0.1g/kg)was injected intraperitoneally 1 hour before inducing ANP.Rats were killed by abdominal aorta exsanguination at 3h,6h and 12h after pancreatitis induced. The histopathological changes of pancreatic and pulmonary tissue were evaluated with microscope.The activation of NF-κB and Caspase-3 in pulmonary tissues were detected by immunohistochemical method. The contents of serum TNF-α,ICAM-1 were measured by ELISA. The expression of NF-κB p65mRNA in pulmonary tissue was measured by RT-PCR and the levels of myeloperoxidase(MPO) in the pulmonary tissue were measured by zymohistochemistry.Results: (1)The severity of pancreas and lung injury was significantly increased in the ANP group than the control group,and that in the ALA-pretreated group was significantly decreased than the former.Meanwhile,the pathological scores of pancreatic and pulmonary tissue in the ANP group were significantly increased than the control group(P<0.05),also that in the ALA-pretreated group significantly decreased at three time points, compared with ANP group(P<0.05).(2)The expression of NF-κB and Caspase-3 in the pulmonary tissue were increased significantly in ANP group than the control group(P<0.05), and in the ALA-pretreated group,the expression of NF-κB and Caspase-3 were significantly decreased compared with ANP group at 6h,12h after intervention(P<0.05).But there were no statistical difference at 3h(P>0.05).(3)The levels of TNF-α,ICAM-1 in serum were increased significantly in ANP group than the control group(P<0.05),and compared with the ANP group, the levels of TNF-αin serum were significantly decreased in the ALA-pretreated group(P<0.05), while the levels of ICAM-1 in serum were decreased significantly at 6h and 12h(P<0.05).(4)The expression of NF-κB p65mRNA in pulmonary tissue in ANP group was significantly higher at 3h,6h,12h compared with control group(P<0.05),and in the ALA-pretreated group the expression was significantly decreased at 6h and 12h compared with ANP group (P<0.05).(5)The levels of MPO in pulmonary tissue in ANP group were higher at 3h compared with those in the control group, but has no significant(P=0.07),and those were significantly increased at 6h and 12h(P<0.05); And in the ALA-pretreated group,the levels of MPO were significantly decreased compared with ANP group(P<0.05).Conclusion: The signal of NF-κB was rapidly activated after operation in lung injury induced by ANP.ALA have protection on the lung injury through the inhibition of the activition of NF-κB by decreasing the production of inflammatory mediators as well as the apoptosis of the lung parenchyma cells.